Synthetic GM1 improves motor and memory dysfunctions in mice with monoallelic or biallelic disruption of GM3 synthase.

This study attempts to answer the question of whether mice with biallelic and monoallelic disruption of the St3gal5 (GM3 synthase) gene might benefit from GM1 replacement therapy. The GM3 produced by this sialyltransferase gives rise to downstream GD3 and the ganglio-series of gangliosides. The latter includes the a-series (GM1 + GD1a), which has proved most essential for neuron survival and function (especially GM1, for which GD1a provides a reserve pool). These biallelic mice serve as a model for children with this relatively rare autosomal recessive condition (ST3GAL5-/-) who suffer rapid neurological decline including motor loss, intellectual disability, visual and hearing loss, failure to thrive, and other severe conditions leading to an early death by 2-5 years of age without supportive care. Here, we studied both these mice, which serve as a model for the parents and close relatives of these children who are likely to suffer long-term disabilities due to partial deficiency of GM1, including Parkinson's disease (PD). We find that the movement and memory disorders manifested by both types of mice can be resolved with GM1 application. This suggests the potential therapeutic value of GM1 for disorders stemming from GM1 deficiency, including GM3 synthase deficiency and PD. It was noteworthy that the GM1 employed in these studies was synthetic rather than animal brain-derived, reaffirming the therapeutic efficacy of the former.

Demographic, social, and behavioral correlates of SARS-CoV-2 seropositivity in a representative, population-based study of Minnesota residents.

BACKGROUND: Monitoring COVID-19 infection risk in the general population is a public health priority. Few studies have measured seropositivity using representative, probability samples. The present study measured seropositivity in a representative population of Minnesota residents prior to vaccines and assess the characteristics, behaviors, and beliefs of the population at the outset of the pandemic and their association with subsequent infection. METHODS: Participants in the Minnesota COVID-19 Antibody Study (MCAS) were recruited from residents of Minnesota who participated in the COVID-19 Household Impact Survey (CIS), a population-based survey that collected data on physical health, mental health, and economic security information between April 20 and June 8 of 2020. This was followed by collection of antibody test results between December 29, 2020 and February 26, 2021. Demographic, behavioral, and attitudinal exposures were assessed for association with the outcome of interest, SARS-CoV-2 seroprevalence, using univariate and multivariate logistic regression. RESULTS: Of the 907 potential participants from the CIS, 585 respondents then consented to participate in the antibody testing (64.4% consent rate). Of these, results from 537 test kits were included in the final analytic sample, and 51 participants (9.5%) were seropositive. The overall weighted seroprevalence was calculated to be 11.81% (95% CI, 7.30%-16.32%) at of the time of test collection. In adjusted multivariate logistic regression models, significant associations between seroprevalence and the following were observed; being from 23-64 and 65+ age groups were both associated with higher odds of COVID-19 seropositivity compared to the 18-22 age group (17.8 [1.2-260.1] and 24.7 [1.5-404.4] respectively). When compared to a less than $30k annual income reference group, all higher income groups had significantly lower odds of seropositivity. Reporting practicing a number of 10 (median reported value in sample) or more of 19 potential COVID-19 mitigation factors (e.g. handwashing and mask wearing) was associated with lower odds of seropositivity (0.4 [0.1-0.99]) Finally, the presence of at least one household member in the age range of 6 to 17 years old was associated with higher odds of seropositivity (8.3 [1.2-57.0]). CONCLUSIONS: The adjusted odds ratio of SARS-CoV-2 seroprevalence was significantly positively associated with increasing age and having household member(s) in the 6-17 year age group, while increasing income levels and a mitigation score at or above the median were shown to be significantly protective factors.

COVID-19 Vaccine Hesitancy in a Population-Based Study of Minnesota Residents.

COVID-19 continues to be a public health concern in the United States. Although safe and effective vaccines have been developed, a significant proportion of the US population has not received a COVID-19 vaccine. This cross-sectional study aimed to describe the demographics and behaviors of Minnesota adults who have not received the primary series of the COVID-19 vaccine, or the booster shot using data from the Minnesota COVID-19 Antibody Study (MCAS) collected through a population-based sample between September and December 2021. Data were collected using a web-based survey sent to individuals that responded to a similar survey in 2020 and their adult household members. The sample was 51% female and 86% White/Non-Hispanic. A total of 9% of vaccine-eligible participants had not received the primary series and 23% of those eligible to receive a booster had not received it. Older age, higher education, better self-reported health, $75,000 to $100,000 annual household income, mask-wearing, and social distancing were associated with lower odds of hesitancy. Gender, race, and previous COVID-19 infection were not associated with hesitancy. The most frequently reported reason for not receiving a COVID-19 vaccination was safety concerns. Mask-wearing and being age 65 or older were the only strong predictors of lower odds of vaccine hesitancy for both the primary series and booster analyses.